The effect of inhibitors of DNA-dependent RNA synthesis (sibiromycin and actinomycin D) and radio toxic doses of 3H-uridine on the bone marrow stem hemopoietic cells in adult mice was studied by means of spleen colonies. The short-term in vitro preincubation of the bone marrow cell suspension with the antibiotics and 3H-uridine resulted in the practically complete inhibition of colony formation. The bone marrow stem hemopoietic cells incorporated 3H-uridine intensively. In the normal adult animals the number of stem cells with the high level of RNA synthesis attained 40% whereas the rest 60% of cells were capable to activate the ribonucleic metabolism upon their in vitro preincubation.

The main types of side reactions due to antibiotic therapy are described. The antibiotic groups most often being the cause of side reactions are presented. Dependence of the toxic (organotropic) effect of antibiotics on the therapy scheme, age and pathological changes in the mechanism of their excretion is indicated. The biochemical mechanisms of the side and selective effects of antibiotics are discussed.

It was found autoradiographically that karminomycin in the therapeutic dose (0.7 mg/kg) significantly hindered cell proliferation of ascitic tumour L-1210, if the cells were at the stage of DNA proliferation during the drug administration. It was shown that karminomycin in a dose of 0.35 mg/kg administered intraperitoneally decreased the number of the leukemic cell of ascitic tumour P-388 by more than 2 times. Then the number of the leukemic cells increased and it doubled during 47 hours. Karminomycin in a dose of 0.7 mg/kg hindered leukemic cell proliferation during 120 hours. The effectiveness of karminomycin therapy in combination with phopurin or cyclophosphan depended on the treatment regimen. Potentiation of the antileukemic effect was noted in the simultaneus use of the drug or in the primary use of cerminomycin 2 hours before administration of phopurin or cyclophosphan. When phopurin or cyclophosphan was used 2 hours before administration of karminomycin, therapeutic effectiveness was lower.

The effect of 2 anthracycline antibiotics, i.e. rubomycin and karminomycin on the content of glycogen, RNA and DNA in the cardiac muscle of albino mice was studied on their five-fold intravenous administration once every 5 days in equieffect doses by the lethal outcome. It was found that under the effect of the above antibiotics accumulation of glycogen in the cardiac muscle of mice took place, this was most pronounced in the animals treated with karminomycin in doses of 2.15 mg/kg. A decrease in the absolute content of RNA and DNA in the mouse heart after the first 4 administrations and in the ratio of RNA to DNA was observed as compared to the analogous values in the control animals at the account of a more intensive decrease in the content of RNA than that of DNA.

A culture of a new actinomycetous species, Nocardiopsis syrinage was isolated from a soil sample. The antibiotic produced by it was named nocamycin. It accumulated in the culture fluid on cultivation of the organism in a nutrient medium containing soybean meal, glycerin, sodium chloride and calcium carbonate. Crystalline nocamycin had an antitumor effect. In inhibited by 72--73 per cent the development of an intraperitoneally implanted lymphadenosis of strain NK/LI in mice.

The inhibitory effect of antibiotic PSX-1 on tumour cells was studied in vitro and in vivo. The antibiotic inhibited above all the utilization of the added 14C-labelled uridine and adenine in EAC cells. After a short exposure to PSX-1 (180 min) the synthesis of nucleic acids and proteins in EAC proliferating in vitro was suppressed. Antibiotic PSX-1 in concentrations of about 2.5 mg/ml showed relatively low toxicity on normal human fibroblasts but caused a marked cytotoxic and cytopathic effect on tumour cells. A potential antitumor effect of PSX-1 was evaluated in vivo by using gradually EAC and L 1210 tumours. All the animals treated with the antibiotic in doses of 2.5--5.0 mg/kg/day with the use of EAC and 5.0 mg/kg/day with the use of L 1210 survived for 90 and 40 days respectively and no tumours developed in the treated mice during this period.

Studies with the use of intact inbred albino mice showed that in intravenous administration the acute toxicity of antibiotic No. 6270 and echinomycin in complexes with DNA increased 3--4 times as compared to the toxicity of the same antibiotics used without the complex. Under the experimental conditions with 3-fold intravenous administration at 72-hour intervals in doses equivalent by their acute toxicity, the antitumor activity of the echinomycin complex with DNA against the solid form of lymphosarcoma L10-1 was approximately 4 times lower than the activity of the antibiotic used alone. Like echinomycin, antibiotic No. 6270 in complex with DNA used according to the same administration scheme in doses equivalent by their acute toxicity had a lower inhibitory effect on growth of lymphosarcoma L10-1 and sarcoma 180 as compared to its use alone.

The application of the lysosome enzymes (acid DNAase, RNAse phosphatase) on the 13th day of pregnancy resulted in the distinct embryolethal effect and the appearance of development abnormalities in the rat embryos. The labilisators of the lysosome membrane weaken the teratogenic activity of the chemical agents whereas the stabilisators strengthen it.

The cytostatic effect of endoxan, Tiotef, bleomycin and other drugs was increased by addition of a thioloprovic compound of N-ethylenmaleimide (N-EM) to the cultures of cancer cells in doses not affecting the synthesis of nucleic acids in these cultures. The sensibilizing effect of N-EM against the antitumor drugs was due to blocking of SH-enzymes responsible of synthesis or reparation of DNA. Thus, a simultaneous effect of N-EM on the thiol cycle and synthesis of nucleic acids was synergistic for a number of antitumor drugs. It provided an increased effect of the cytostatics in doses having no activity under conditions of routine in vitro tests.

The Nereis virens embryos at the stages of 2, 8, 16 and 32 blastomeres end of cleavage and beginning of rotation were placed in the actinomycin D or sibiromycin solutions and the effect of antibiotics on 3H-thymidine incorporation during cleavage, at the beginning of rotation and in trochophore was determined by means of autoradiography after careful washing the embryos off. Under the effect of actinomycin D the intensity of 3H-thymidine incorporation during cleavage decreased insignificantly, at the gastrula stage somewhat exceeded that in the control, and at the stages of trochophore formation decreased twice. At the later stages it approached the normal level. In the experiments with sibiromycin which proved to have more distinct inhibitory effect, the stage of trochophore formation was also found to be the most sensitive to the antibiotic.

An actinomycetes strain 792 producing a new antibiotic was isolated under the programme of antitumor antibiotic screening. By its morphological and cultural properties strain 792 was classified as belonging to species Actinomyces bottropensis. Antibiotic 792 was recovered from the culture fluid of the strain by the extraction method in the form of a crystalline orange substances. lambda max 235, 305, 410 nm (E 1% 1cm 705, 105, 168), m. p. 232-255 degrees (dec), molecular weight 340, C 67 per cent, H 4.8 per cent, no nitrogen, sulphur or halogens. The antibiotic was inactivated in alkaline solutions forming a hardly soluble compound crystallizing in the form of red needles, lambda max 256, 485 nm (E 1% 1ct 800, 195), m. p. 202-204 degrees (dec), molecular weight 320, C 69.5 per cent, H 4.7 per cent. Antibiotic 792 had antitumor and antimicrobial activity.

Intravesical instillations of 10% dibunol liniment were used for the treatment of 132 patients with bladder tumors. An objective improvement was noted in 62.4%, including considerable lessening of the tumor size in 20% and its disappearance in 8.8% of patients. An efficacy of the treatment was considerably greater in bladder cancer in stages T1--T2 than in stages T3 and T4. The frequency of bladder cancer recurrence is found to be lowered following surgery associated with application of dibunol, also the manifest antiinflammatory activity of the drug is emphasized. No side effects relative to the toxic action of dibunol were observed. The use of dibunol seems to be rational in patients with bladder tumors of early stages, especially if associated with surgical therapy, and in tumor recurrences, and also with the symptomatic purposes in inoperable patients.

An observation of a polymorphnocellular variant of pseudolymphomatosis of the stomach diagnosed retrospectively is described. Initially, the case was treated as lymphogranulomatosis of the stomach, and in connection with the latter the patient was given long-term immunodepressive therapy. At autopsy (6 years later) atrophy of the lymphoreticular tissue and mucinous carcinoma of the stomach were revealed. The authors hold that the second tumour developed against the background of the immuno-depressive therapy, whereas at the beginning the condition was pseudolymphomatosis.